time is shortened (positive lusitropic effect). Systolic blood pressure is modestly augmented and diastolic blood pressure is decreased. The resultant widened pulse pressure reflects the combined effects of the increased stroke volume and the reduction in systemic vascular resistance secondary to blood vessel dilation in skin, muscle, and heart. These effects in turn are partly due to the increase in tissue production of heat and CO2 that thyroid hormone induces (see on Basal Metabolic Rate and Thermogenesis). In addition, however, thyroid hormone decreases systemic resistance by dilating arterioles in the peripheral circulation. Total blood volume is increased by activation of the renin-angiotensinaldosterone axis, thereby increasing renal tubular sodium reabsorption (see
The cardiac inotropic effects of T3 are both direct and indirect. The latter are due primarily to enhanced responsiveness to catecholamines (see ). Direct inotropic effects (see
Fig. 42.11 ) involve regulation of multiple proteins that enhance contractility, including increased α-myosin heavy chain expression and inhibition of the plasma membrane Na+/Ca++ exchanger. Sarcoplasmic reticulum Ca++-ATPase (SERCA) is increased by T3, whereas phospholamban is decreased. As a result, sequestration of calcium during diastole is enhanced and the relaxation time is shortened. Increased ryanodine Ca++ channels in the sarcoplasmic reticulum promote release of Ca++ from the sarcoplasmic reticulum during systole.
Thyroidhormonelevelsinthenormalrangearenecessaryforoptimumcardiacperformance.Adeficiencyofthyroidhormoneinhumansreducesstrokevolume,leftventricularejectionfraction,cardiacoutput,andtheefficiencyofcardiacfunction.Thelatterdefectisshownbythefactthatthestrokeworkindex[(strokevolume/leftventricularmass)× peaksystolicbloodpressure]isdecreasedtoagreaterextentthanmyocardialoxidativemetabolism.Theriseinsystemicvascularresistancemaycontributetothiscardiacdebility.Incontrast,excessthyroidhormoneenhancescardiacoutputbyincreasingbothheartrateandstrokevolume.Pulsepressureiswidenedbyincreasedsystolicpressureanddecreaseddiastolicpressureduetodecreasedsystemicvascularresistance.Thyrotoxicosisisassociatedwithpalpitations,atrialfibrillation,andmitralvalveprolapse(see
Increased O2 use ultimately depends on an increased supply of substrates for oxidation. T3 augments glucose absorption from the gastrointestinal tract and increases glucose turnover (glucose uptake, oxidation, and synthesis). In adipose tissue, thyroid hormone induces enzymes for the synthesis of fatty acids, including acetyl-CoA carboxylase and fatty acid synthase, and enhances lipolysis by increasing the number of β-adrenergic receptors (see the Autonomic Nervous System ). Thyroid hormone also enhances the clearance of chylomicrons. Thus lipid turnover (free fatty acid release from adipose tissue and oxidation) is augmented.
Protein turnover (release of muscle amino acids, protein degradation, and to a lesser extent protein synthesis and urea formation) is also increased. T3 potentiates the respective stimulatory effects of epinephrine, norepinephrine, glucagon, cortisol, and growth hormone on gluconeogenesis,